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  1. Article: The life and vision of a pioneer: a tribute to Tage Astrup, D.Sc., Dr.Med.h.c.

    Kwaan, Hau C

    Seminars in thrombosis and hemostasis

    2007  Volume 33, Issue 4, Page(s) 299–300

    MeSH term(s) Biomedical Research/history ; Fibrinolysis/physiology ; History, 20th Century
    Language English
    Publishing date 2007-06
    Publishing country United States
    Document type Biography ; Historical Article ; Journal Article
    ZDB-ID 196901-8
    ISSN 1098-9064 ; 0094-6176
    ISSN (online) 1098-9064
    ISSN 0094-6176
    DOI 10.1055/s-2007-976180
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  2. Article: The Life and Vision of a Pioneer: A Tribute to Tage Astrup, D.Sc., Dr.Med.h.c.

    Kwaan, Hau C

    Seminars in Thrombosis and Hemostasis

    (Hemostatic Dysfunction in Malignant Hematologic Disorders)

    2007  Volume 33, Issue 04, Page(s) 299–300

    Series title Hemostatic Dysfunction in Malignant Hematologic Disorders
    Language English
    Publishing date 2007-05-24
    Publishing place Stuttgart ; New York
    Document type Article
    ZDB-ID 196901-8
    ISSN 1098-9064 ; 0094-6176
    ISSN (online) 1098-9064
    ISSN 0094-6176
    DOI 10.1055/s-2007-976180
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  3. Article ; Online: P2Y12 inhibitor use predicts hematoma expansion in patients with intracerebral hemorrhage.

    Houskamp, Ethan J / Liu, Yuzhe / Silva Pinheiro do Nascimento, Juliana / Jahromi, Babak S / Lindholm, Paul F / Kwaan, Hau C / Naidech, Andrew M

    Annals of clinical and translational neurology

    2024  

    Abstract: ... performed with Kruskal-Wallis H, and correction for multiple comparisons performed with Dunn's test ...

    Abstract Objective: Hematoma expansion (HE) predicts disability and death after acute intracerebral hemorrhage (ICH). Aspirin and anticoagulants have been associated with HE. We tested the hypothesis that P2Y12 inhibitors predict subsequent HE in patients. We explored laboratory measures of P2Y12 inhibition and dual antiplatelet therapy with aspirin (DAPT).
    Methods: We prospectively identified patients with ICH. Platelet activity was measured with the VerifyNow-P2Y12 assay. Hematoma volumes for initial and follow-up CTs were calculated using a validated semi-automated technique. HE was defined as the difference between hematoma volumes on the initial and follow-up CT scans. Nonparametric statistics were performed with Kruskal-Wallis H, and correction for multiple comparisons performed with Dunn's test.
    Results: In 194 patients, 15 (7.7%) were known to take a P2Y12 inhibitor (clopidogrel in all but one). Patients taking a P2Y12 inhibitor had more HE compared to patients not taking a P2Y12 inhibitor (3.5 [1.2-11.9] vs. 0.1 [-0.8-1.4] mL, p = 0.004). Patients taking DAPT experienced the most HE (7.2 [2.6-13.8] vs. 0.0 [-1.0-1.1] mL, p = 0.04). The use of P2Y12 inhibitors was associated with less P2Y12 activity (178 [149-203] vs. 288 [246-319] P2Y12 reaction units, p = 0.005).
    Interpretation: Patients taking a P2Y12 inhibitor had more HE and less P2Y12 activity. The effect was most pronounced in patients on DAPT, suggesting a synergistic effect of P2Y12 inhibitors and aspirin with respect to HE. Acute reversal of P2Y12 inhibitors in acute ICH requires further study.
    Language English
    Publishing date 2024-04-23
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2740696-9
    ISSN 2328-9503 ; 2328-9503
    ISSN (online) 2328-9503
    ISSN 2328-9503
    DOI 10.1002/acn3.52070
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  4. Article ; Online: IgG hexamers initiate complement-dependent acute lung injury.

    Cleary, Simon J / Seo, Yurim / Tian, Jennifer J / Kwaan, Nicholas / Bulkley, David P / Bentlage, Arthur E H / Vidarsson, Gestur / Boilard, Éric / Spirig, Rolf / Zimring, James C / Looney, Mark R

    The Journal of clinical investigation

    2024  

    Abstract: Antibodies can initiate lung injury in a variety of disease states such as autoimmunity, transfusion reactions, or after organ transplantation, but the key factors determining in vivo pathogenicity of injury-inducing antibodies are unclear. Harmful ... ...

    Abstract Antibodies can initiate lung injury in a variety of disease states such as autoimmunity, transfusion reactions, or after organ transplantation, but the key factors determining in vivo pathogenicity of injury-inducing antibodies are unclear. Harmful antibodies often activate the complement cascade. A model for how IgG antibodies trigger complement activation involves interactions between IgG Fc domains driving assembly of IgG hexamer structures that activate C1 complexes. The importance of IgG hexamers in initiating injury responses was unclear, so we tested their relevance in a mouse model of alloantibody and complement-mediated acute lung injury. We used three approaches to block alloantibody hexamerization (antibody carbamylation, the K439E Fc mutation, or treatment with domain B from Staphylococcal protein A), all of which reduced acute lung injury. Conversely, Fc mutations promoting spontaneous hexamerization made a harmful alloantibody into a more potent inducer of acute lung injury and rendered an innocuous alloantibody pathogenic. Treatment with a recombinant Fc hexamer 'decoy' therapeutic protected mice from lung injury, including in a model with transgenic human FCGR2A expression that exacerbated pathology. These results indicate an in vivo role of IgG hexamerization in initiating acute lung injury and the potential for therapeutics that inhibit or mimic hexamerization to treat antibody-mediated diseases.
    Language English
    Publishing date 2024-03-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI178351
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  5. Article: IgG hexamers initiate acute lung injury.

    Cleary, Simon J / Seo, Yurim / Tian, Jennifer J / Kwaan, Nicholas / Bulkley, David P / Bentlage, Arthur E H / Vidarsson, Gestur / Boilard, Éric / Spirig, Rolf / Zimring, James C / Looney, Mark R

    bioRxiv : the preprint server for biology

    2024  

    Abstract: Antibodies can initiate lung injury in a variety of disease states such as autoimmunity, transfusion reactions, or after organ transplantation, but the key factors determining in vivo pathogenicity of injury-inducing antibodies are unclear. A previously ... ...

    Abstract Antibodies can initiate lung injury in a variety of disease states such as autoimmunity, transfusion reactions, or after organ transplantation, but the key factors determining in vivo pathogenicity of injury-inducing antibodies are unclear. A previously overlooked step in complement activation by IgG antibodies has been elucidated involving interactions between IgG Fc domains that enable assembly of IgG hexamers, which can optimally activate the complement cascade. Here, we tested the in vivo relevance of IgG hexamers in a complement-dependent alloantibody model of acute lung injury. We used three approaches to block alloantibody hexamerization (antibody carbamylation, the K439E Fc mutation, or treatment with domain B from Staphylococcal protein A), all of which reduced acute lung injury. Conversely, Fc mutations promoting spontaneous hexamerization made a harmful alloantibody into a more potent inducer of acute lung injury and rendered an innocuous alloantibody pathogenic. Treatment with a recombinant Fc hexamer 'decoy' therapeutic protected mice from lung injury, including in a model with transgenic human FCGR2A expression that exacerbated pathology. These results indicate a direct in vivo role of IgG hexamerization in initiating acute lung injury and the potential for therapeutics that inhibit or mimic hexamerization to treat antibody-mediated diseases.
    Language English
    Publishing date 2024-01-27
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.01.24.577129
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The coagulopathy in acute promyelocytic leukaemia--what have we learned in the past twenty years.

    Kwaan, Hau C / Cull, Elizabeth H

    Best practice & research. Clinical haematology

    2014  Volume 27, Issue 1, Page(s) 11–18

    Abstract: Coagulopathy is a unique component of the pathology of acute promyelocytic leukaemia (APL). Though many causative factors have been elucidated, therapies to rectify the coagulopathy are far from being realised. Thrombotic and bleeding complications ... ...

    Abstract Coagulopathy is a unique component of the pathology of acute promyelocytic leukaemia (APL). Though many causative factors have been elucidated, therapies to rectify the coagulopathy are far from being realised. Thrombotic and bleeding complications remain the major causes of early deaths. In this chapter, the known causes of abnormalities in haemostatic function, namely the coagulopathy and changes in the fibrinolytic system, will be reviewed. Major risk factors for these complications are identified. Current available measures for correction of the coagulopathy and their effectiveness are critically examined. Unless the coagulopathy can be effectively controlled, bleeding complications will remain an obstacle to achieving a cure for this disease. The issues that need to be addressed in next phase of investigations are also discussed.
    MeSH term(s) Annexin A2/blood ; Anticoagulants/therapeutic use ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Arsenicals/pharmacology ; Arsenicals/therapeutic use ; Blood Coagulation Disorders/drug therapy ; Blood Coagulation Disorders/etiology ; Blood Coagulation Tests ; Carboxypeptidase B2/deficiency ; Disseminated Intravascular Coagulation/etiology ; Fibrinolysis ; Forecasting ; Granulocyte Precursor Cells/metabolism ; Hemorrhagic Disorders/drug therapy ; Hemorrhagic Disorders/etiology ; Humans ; Leukemia, Promyelocytic, Acute/blood ; Leukemia, Promyelocytic, Acute/complications ; Leukemia, Promyelocytic, Acute/drug therapy ; Oxides/pharmacology ; Oxides/therapeutic use ; Recombinant Proteins/therapeutic use ; Risk Factors ; S100 Proteins/blood ; Thrombomodulin/therapeutic use ; Thrombophilia/drug therapy ; Thrombophilia/etiology ; Thromboplastin/metabolism ; Tretinoin/therapeutic use ; Urokinase-Type Plasminogen Activator/blood
    Chemical Substances ANXA2 protein, human ; Annexin A2 ; Anticoagulants ; Antineoplastic Agents ; Arsenicals ; Oxides ; Recombinant Proteins ; S100 Proteins ; S100 calcium binding protein A10 ; THBD protein, human ; Thrombomodulin ; Tretinoin (5688UTC01R) ; Thromboplastin (9035-58-9) ; Carboxypeptidase B2 (EC 3.4.17.20) ; Urokinase-Type Plasminogen Activator (EC 3.4.21.73) ; arsenic trioxide (S7V92P67HO)
    Language English
    Publishing date 2014-03
    Publishing country Netherlands
    Document type Journal Article ; Review
    ZDB-ID 2048027-1
    ISSN 1532-1924 ; 1521-6926
    ISSN (online) 1532-1924
    ISSN 1521-6926
    DOI 10.1016/j.beha.2014.04.005
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  7. Article: A Case Series of Thromboelastography-Guided Anticoagulation in COVID-19 Patients with Inherited and Acquired Hypercoagulable States.

    Thomas, Anthony V / Lin, Kevin P / Stillson, John E / Bunch, Connor M / Speybroeck, Jacob / Wiarda, Grant / Al-Fadhl, Hamid / Gillespie, Laura / Zamlut, Mahmud / Fulkerson, Daniel H / Khan, Rashid Z / Kwaan, Hau C / Walsh, Mark M

    Case reports in medicine

    2021  Volume 2021, Page(s) 5568982

    Abstract: One of the complications of the novel coronavirus disease 2019 (COVID-19) is hypercoagulability. For this reason, patients presenting with COVID-19 are often put on therapeutic or intermediate anticoagulation upon hospitalization. A common issue of this ... ...

    Abstract One of the complications of the novel coronavirus disease 2019 (COVID-19) is hypercoagulability. For this reason, patients presenting with COVID-19 are often put on therapeutic or intermediate anticoagulation upon hospitalization. A common issue of this anticoagulation is the progression to hypocoagulability resulting in hemorrhage. Therefore, monitoring the hemostatic integrity of critically ill COVID-19 patients is of utmost importance. In this case series, we present the cases of three coagulopathic COVID-19 patients whose anticoagulation was guided by thromboelastography (TEG). In each case, TEG permitted the clinical team to simultaneously prevent thrombotic and hemorrhagic events, a difficult task for COVID-19 patients admitted to the intensive care unit. The first two cases illustrate the utility of TEG to guide anticoagulant dosing for COVID-19 patients when the activated partial thromboplastin time (aPTT) is inaccurate. The first case was a severely ill COVID-19 patient with end-stage renal disease and a falsely elevated aPTT secondary to hypertriglyceridemia. The second case was a severely ill COVID-19 patient with chronic pulmonary disease who demonstrated a falsely elevated aPTT due to polycythemia and hemoconcentration. In both cases, TEG was sensitive to the hypercoagulability caused by the metabolic derangements which enabled the goal-directed titration of anticoagulants. The last case depicts a severely ill COVID-19 patient with an inherited factor V Leiden mutation who required abnormally high dosing to achieve therapeutic anticoagulation, guided by TEG. Hypercoagulopathic COVID-19 patients are difficult to anticoagulate without development of hypocoagulopathy. Treatment of these patients demands goal-directed therapy by diligent laboratory monitoring. This can be accomplished by the use of TEG coupled with aPTT to guide anticoagulation. This case series illustrates the necessity for active hemostatic monitoring of critically ill COVID-19 patients.
    Language English
    Publishing date 2021-07-31
    Publishing country United States
    Document type Case Reports
    ZDB-ID 2502642-2
    ISSN 1687-9635 ; 1687-9627
    ISSN (online) 1687-9635
    ISSN 1687-9627
    DOI 10.1155/2021/5568982
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  8. Article ; Online: Thromboelastography-Guided Anticoagulant Therapy for the Double Hazard of Thrombohemorrhagic Events in COVID-19: A Report of 3 Cases.

    Bunch, Connor M / Thomas, Anthony V / Stillson, John E / Gillespie, Laura / Lin, Kevin P / Speybroeck, Jacob / Kwaan, Hau C / Fulkerson, Daniel H / Zamlut, Mahmud / Khan, Rashid / Walsh, Mark M

    The American journal of case reports

    2021  Volume 22, Page(s) e931080

    Abstract: BACKGROUND The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), often manifests a coagulopathy in severely ill patients, which may cause hemorrhage and/or thrombosis of varying ... ...

    Abstract BACKGROUND The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), often manifests a coagulopathy in severely ill patients, which may cause hemorrhage and/or thrombosis of varying severity. This report comprises the cases of 3 patients with COVID-19-associated coagulopathy who were evaluated with thromboelastography (TEG) and activated partial thromboplastin time (aPTT) to enable personalized anticoagulant therapy. CASE REPORT Three patients presented with COVID-19 pneumonia, confirmed by reverse transcription-polymerase chain reaction, who developed thrombohemorrhagic coagulopathy.Case 1: A 72-year-old woman on long-term warfarin therapy for a history of venous thromboembolism developed a right upper lobe pulmonary embolus, despite an international normalized ratio of 6.4 and aPTT of 120.7 s. TEG enabled successful anticoagulation with heparin, and her pulmonary infarct was no longer present 2 weeks later.Case 2: A 55-year-old woman developed a rectus sheath hematoma while on heparin, and TEG demonstrated increased fibrinolysis despite COVID-19 patients more commonly undergoing fibrinolytic shutdown.Case 3: A 43-year-old woman had significant thrombus burden while severely hypocoagulable according to laboratory testing. As the venous thrombi enlarged in a disseminated intravascular coagulopathic-like state, the heparin dose was escalated to achieve a target aPTT of 70 to 80 s, resulting in a flat line TEG tracing. CONCLUSIONS These 3 cases of COVID-19 pneumonia with complex and varied clinical histories demonstrated the clinical value of TEG combined with the measurement of aPTT to facilitate personalized anticoagulation, resulting in good clinical outcomes.
    MeSH term(s) Adult ; Aged ; Anticoagulants/therapeutic use ; COVID-19/complications ; Female ; Hemorrhage/drug therapy ; Hemorrhage/virology ; Heparin/therapeutic use ; Humans ; Middle Aged ; Thrombelastography ; Thrombolytic Therapy ; Thrombosis/drug therapy ; Thrombosis/virology
    Chemical Substances Anticoagulants ; Heparin (9005-49-6)
    Language English
    Publishing date 2021-04-01
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 2517183-5
    ISSN 1941-5923 ; 1941-5923
    ISSN (online) 1941-5923
    ISSN 1941-5923
    DOI 10.12659/AJCR.931080
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Thromboelastography-Guided Management of Anticoagulated COVID-19 Patients to Prevent Hemorrhage.

    Stillson, John E / Bunch, Connor M / Gillespie, Laura / Khan, Rashid / Wierman, Meredith / Pulvirenti, Joseph / Phyu, Htay / Anderson, Stephen / Al-Fadhl, Mahmoud / Thomas, Anthony V / Kwaan, Hau C / Moore, Ernest / Moore, Hunter / Walsh, Mark M

    Seminars in thrombosis and hemostasis

    2021  Volume 47, Issue 4, Page(s) 442–446

    MeSH term(s) Adult ; Aged ; Aged, 80 and over ; Algorithms ; Anticoagulants/administration & dosage ; Anticoagulants/adverse effects ; Anticoagulants/therapeutic use ; Blood Coagulation Tests ; Blood Proteins/analysis ; COVID-19/blood ; COVID-19/complications ; COVID-19/therapy ; Clinical Protocols ; Critical Care ; Drug Monitoring/methods ; Enoxaparin/administration & dosage ; Enoxaparin/adverse effects ; Enoxaparin/therapeutic use ; Female ; Hemorrhage/chemically induced ; Hemorrhage/prevention & control ; Heparin/administration & dosage ; Heparin/adverse effects ; Heparin/therapeutic use ; Humans ; Male ; Middle Aged ; Point-of-Care Testing ; Postoperative Complications/epidemiology ; Prospective Studies ; Respiration, Artificial ; Risk Factors ; SARS-CoV-2 ; Thrombelastography ; Thrombophilia/drug therapy ; Thrombophilia/etiology
    Chemical Substances Anticoagulants ; Blood Proteins ; Enoxaparin ; Heparin (9005-49-6)
    Language English
    Publishing date 2021-02-19
    Publishing country United States
    Document type Comparative Study ; Journal Article
    ZDB-ID 196901-8
    ISSN 1098-9064 ; 0094-6176
    ISSN (online) 1098-9064
    ISSN 0094-6176
    DOI 10.1055/s-0041-1723754
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  10. Article ; Online: The Choice between Plasma-Based Common Coagulation Tests and Cell-Based Viscoelastic Tests in Monitoring Hemostatic Competence: Not an either-or Proposition.

    Bunch, Connor M / Berquist, Margaret / Ansari, Aida / McCoy, Max L / Langford, Jack H / Brenner, Toby J / Aboukhaled, Michael / Thomas, Samuel J / Peck, Ethan / Patel, Shivani / Cancel, Emily / Al-Fadhl, Mahmoud D / Zackariya, Nuha / Thomas, Anthony V / Aversa, John G / Greene, Ryan B / Seder, Christopher W / Speybroeck, Jacob / Miller, Joseph B /
    Kwaan, Hau C / Walsh, Mark M

    Seminars in thrombosis and hemostasis

    2022  Volume 48, Issue 7, Page(s) 769–784

    Abstract: There has been a significant interest in the last decade in the use of viscoelastic tests (VETs) to determine the hemostatic competence of bleeding patients. Previously, common coagulation tests (CCTs) such as the prothrombin time (PT) and partial ... ...

    Abstract There has been a significant interest in the last decade in the use of viscoelastic tests (VETs) to determine the hemostatic competence of bleeding patients. Previously, common coagulation tests (CCTs) such as the prothrombin time (PT) and partial thromboplastin time (PTT) were used to assist in the guidance of blood component and hemostatic adjunctive therapy for these patients. However, the experience of decades of VET use in liver failure with transplantation, cardiac surgery, and trauma has now spread to obstetrical hemorrhage and congenital and acquired coagulopathies. Since CCTs measure only 5 to 10% of the lifespan of a clot, these assays have been found to be of limited use for acute surgical and medical conditions, whereby rapid results are required. However, there are medical indications for the PT/PTT that cannot be supplanted by VETs. Therefore, the choice of whether to use a CCT or a VET to guide blood component therapy or hemostatic adjunctive therapy may often require consideration of both methodologies. In this review, we provide examples of the relative indications for CCTs and VETs in monitoring hemostatic competence of bleeding patients.
    MeSH term(s) Humans ; Hemostatics ; Thrombelastography/methods ; Blood Coagulation Tests ; Hemostasis ; Blood Coagulation Disorders/therapy ; Hemorrhage/therapy
    Chemical Substances Hemostatics
    Language English
    Publishing date 2022-09-29
    Publishing country United States
    Document type Review ; Journal Article
    ZDB-ID 196901-8
    ISSN 1098-9064 ; 0094-6176
    ISSN (online) 1098-9064
    ISSN 0094-6176
    DOI 10.1055/s-0042-1756302
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